Phase 3 · Liraglutide

DUAL I trial results

A 26 Week Randomised, Parallel Three-arm, Open-label, Multi-centre, Multinational Treat-to-target Trial Comparing Fixed Ratio Combination of Insulin Degludec and Liraglutide Versus Insulin Degludec or Liraglutide Alone, in Subjects With Type 2 Diabetes Treated With 1-2 Oral Anti-diabetic Drugs (OADs)With a 26 Week Extension

Mean Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 26. (Percentage of glycosylated haemoglobin), Week 0, week 26. IDeg: -1.44; IDegLira: -1.91; Liraglutide: -1.28.

Participants
1,663
Status
completed
Completed
2012-11-22
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT01336023), updated at source Feb 19, 2018. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What DUAL I measured first

Mean Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 26.Percentage of glycosylated haemoglobin · Week 0, week 26 · mean
IDegn=413IDegLiran=833Liraglutiden=414
-1.44(1.03)-1.91(1.07)-1.28(1.13)
Side effects by arm

Side effects in DUAL I

Percent of participants affected, Adverse events (AEs) were collected from first day of exposure to randomised treatment of 52 weeks (26 week main period + 26 week extension period) + 7 days follow-up after the last day on randomised.... The most common events the registry lists.

EventIDegIDegLiraLiraglutide
Any serious event5.3%4.6%5.8%
Nausea3.9%10.3%22.3%
Diarrhoea6.8%10.2%16.3%
Headache10.9%12.8%14.6%
Nasopharyngitis12.6%13.9%13.3%
Vomiting2.4%5%9%
Lipase increased4.4%5.8%8.5%
Upper respiratory tract infection8.3%7.8%8%
Decreased appetite0.5%2.7%7.3%
Back pain4.9%5.5%5.6%
Dyspepsia1.2%3.4%5.3%
Arthralgia3.6%3.6%5.3%
Dizziness2.4%2.9%5.3%
Constipation1%3.2%5.1%
Secondary outcomes

What else it measured

Mean Change From Baseline in Body Weight at Week 26kg · Week 0, Week 26 · mean
IDegn=413IDegLiran=833Liraglutiden=414
1.6(4.0)-0.5(3.5)-3.0(3.5)
Number of Hypoglycaemic EpisodesEvents per 100 patient years of exposure · Weeks 0-26 · number
IDegn=412IDegLiran=825Liraglutiden=412
256.7180.222.0
Change From Baseline in Incremental Area Under the Curve 0-4h (iAUC0-4h) Derived From the Glucose Concentration Profile During Meal Testmmol/L · Week 0, Week 26 · mean
IDegn=63IDegLiran=128Liraglutiden=61
-0.17(1.98)-0.87(1.65)-0.78(1.62)
Mean Actual Daily Insulin Doseunits · Week 26 · mean
IDegn=408IDegLiran=816
53(28)38(13)
The trial

How DUAL I was run

This trial is conducted globally. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (IDeg) and liraglutide (Lira) in subjects with type 2 diabetes. Subjects are to continue their pre-trial treatment with metformin or metformin + pioglitazone throughout the entire trial.

  • IDeg
  • IDegLira
  • Lira
Who could join the trial

Inclusion Criteria: * Subjects with type 2 diabetes * HbA1c 7.0-10.0 % (both inclusive) with the aim of a median HbA1c of 8.3%. Accordingly, when approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c of below or equal to 8.3%, or when approximately 50% of the randomised subjects have a HbA1c of below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3% * Male or female, age 18 years or above (Taiwan: 20 years or above for a site 653 in Taiwan: Taichung Veterans General Hospital) * Subjects on stable dose of 1-2 OADs (metformin \[at least 1500 mg or max tolerated dose\] or metformin \[at least 1500 mg or max tolerated dose\] + pioglitazone \[at least 30 mg\]) for at least 90 days prior to screening * Body Mass Index (BMI) maximum 40 kg/m\^2 Exclusion Criteria: * Treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator) * Treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (eg exenatide, liraglutide), sulphonylurea or dipeptidyl peptidase 4 (DPP-4) inhibitors within 90 days prior to trial * Impaired liver function, defined as alanine aminotransferese (ALAT) at least 2.5 times Upper Normal Range (UNR) (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive) * Impaired renal function defined as serum-creatinine at least 133 mcmol/l (at least 1.5 mg/dl) for males and at least 125 mcmol/l (at least 1.4) for females, or as allowed according to local contraindications for metformin (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive) * Screening calcitonin at least 50 ng/L * Subjects with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2) * Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months and planned coronary, carotid or peripheral artery revascularisation procedures * Severe uncontrolled treated or untreated hypertension (systolic blood pressure at least 180 mm Hg or diastolic blood pressure at least 100 mm Hg) * Acute treatment required proliferative retinopathy or maculopathy (macular oedema) * History of chronic pancreatitis or idiopathic acute pancreatitis

Published papers

Papers from DUAL I

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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